title: Paeonol induces vasodilatation in rat mesenteric artery via inhibiting extracellular Ca²⁺ influx and intracellular Ca²⁺ release.
abstract: OBJECTIVE
  To investigate the vasodilative effect of paeonol in rat mesenteric artery and the mechanisms responsible for it.
  
  
  METHODS
  Rats were anaesthetized and sacrificed. The superior mesenteric artery was removed, dissected free of adherent tissue and cut into 2.0 mm long cylindrical segments. Isometric tension of artery rings was recorded by a myograph system in vitro. Concentration-relaxation curves of paeonol (17.8 μ mol/L to 3.16 mmol/L) were recorded on artery rings precontracted by potassium chloride (KCl) and concentration-contraction curves of KCl, 5-hydroxytryptamine (5-HT), noradrenaline (NA) or calcium chloride (CaCl2) were recorded in the presence of paeonol (10(-4.5), 10(-3.8), 10(-3.5) mol/L) respectively. And also, concentration-relaxation curves of paeonol were recorded in the presence of different potassium channel inhibitors and propranolol on rings precontracted with KCl respectively. To investigate the role of intracellular Ca(2+) release from Ca(2+) store, the contraction induced by NA (100 μ mol/L) and CaCl2 (2 mmol/L) in Ca(2+) free medium was observed in the presence of paeonol respectively.
  
  
  RESULTS
  Paeonol relaxed artery rings precontracted by KCl in a concentration-dependent manner and the vasodilatation effect was not affected by endothelium denudation. Paeonol significant decreased the maximum contractions (Emax) induced by KCl, CaCl2, NA and 5-HT, as well as Emax induced by NA and CaCl2 in Ca(2+) -free medium, suggesting that paeonol dilated the artery via inhibiting the extracellular Ca(2+) influx mediated by voltage-dependent calcium channel, and receptor-mediated Ca(2+)-influx and release. Moreover, none of glibenclamide, tetraethylammonium, barium chlorded and propranolol affected the paeonol-induced vasodilatation, indicating that the vasodilatation was not contributed to ATP sensitive potassium channel, calcium-activated potassium channel, inwardly rectifying potassium channel, and β-adrenoceptor.
  
  
  CONCLUSIONS
  Paeonol induces non-endothelium dependent-vasodilatation in rat mesenteric artery via inhibiting voltage-dependent calcium channel-mediated extracellular Ca(2+) influx and receptor-mediated Ca(2+) influx and release.
authors.affiliation: Experiment and Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. jinyanz@163.com
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Weng
authors.forename: Yi-Kui
authors.initials: YK
authors.lastname: Li
authors.forename: Le
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000098:Acetophenones; D000319:Adrenergic beta-Antagonists; D026902:Potassium Channel Blockers; D012701:Serotonin; C013638:paeonol; D011189:Potassium Chloride; D002122:Calcium Chloride; D002118:Calcium; D009638:Norepinephrine